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Biomedical subjects

B Eghtesad

Publications and source records attributed to B Eghtesad.

At least 19 recordsLinked to original sources
PubMed2006

Survival of liver transplant patients coinfected with HIV and HCV is adversely impacted by recurrent hepatitis C.

Although liver transplantation (LTx) in HIV-positive patients receiving highly active antiretroviral therapy (HAART) has been successful, some have reported poorer outcomes in patients coinfected with hepatitis C virus (HCV). Here we discuss the impact of recurrent HCV on 27 HIV-positive patients who underwent LTx. HIV infection was well controlled post-transplantation. Survival in HIV-positive/HCV-positive patients was shorter compared to a cohort of HIV-negative/HCV-positive patients matched in age, model for end-stage liver disease (MELD) score, and time of transplant, with cumulative 1-, 3- and 5-year patient survival of 66.7%, 55.6% and 33.3% versus 75.7%, 71.6% and 71.6%, respectively, although not significantly (p = 0.07), and there was a higher likelihood of developing cirrhosis or dying from an HCV-related complication in coinfected subjects (RR = 2.6, 95% CI, 1.06-6.35; p = 0.03). Risk factors for poor survival included African-American race (p = 0.02), MELD score > 20 (p = 0.05), HAART intolerance postLTx (p = 0.01), and postLTx HCV RNA > 30000000 IU/mL (p = 0.00). Recurrent HCV in 18 patients was associated with eight deaths, including three from fibrosing cholestatic hepatitis. Among surviving coinfected recipients, five are alive at least 3 years after LTx, and of 15 patients treated with interferon-alpha/ribavirin, six (40%) are HCV RNA negative, including four with sustained virological response. Hepatitis C is a major cause of graft loss and patient mortality in coinfected patients undergoing LTx.

Adult↗
PubMed2005

Livers transplanted from donors after cardiac death occurring in the ICU or the operating room have excellent outcomes.

BACKGROUND: Increasing donor hospital cooperation with donation after cardiac death (DCD) requires the organ procurement organization (OPO) to use current withdrawal of life support (WLS) protocols. Hospital ICU nurses/physicians are comfortable performing the emotionally draining procedure of WLS in the ICU while OPOs are reluctant to accept these donors due to increased warm ischemia (WI). In our area, several hospitals will only allow WLS to occur in the ICU. This study compares liver outcomes from DCD donors where death occurred in the ICU (DCDICU) vs the OR (DCDOR). METHODS: From March 2003 to June 2004, 34 DCD donors were recovered by our OPO. WLS occurred in the ICU for 26 donors (76%) and in the OR for 8 donors (24%). Thirteen of 26 DCDICU and 5 of 8 DCDOR livers were transplanted. Donor demographics, warm ischemic time, cold ischemic time, distance shipped, and recipient functions were analyzed. RESULTS: Eighteen livers were transplanted both locally and at distant transplant centers. Results are outlined in the . CONCLUSIONS: Although DCDICU donors averaged approximately 4 minutes longer WI than DCDOR donors, short-term results for both groups were equivalent. These findings support using DCDICU livers. DCDICU donors have the potential to significantly improve donor hospital cooperation.

Adult↗
PubMed2005

Tacrolimus for primary liver transplantation: 12 to 15 years actual follow-up with safety profile.

BACKGROUND: Tacrolimus has been increasingly used for liver transplantation during the last decade. The drug has immunological advantages in short- to medium-term follow-up. However, data on longitudinal follow-up are lacking. AIM: The aim of the present report was to examine the impact of tacrolimus in primary adult and pediatric liver transplantation (LTx) patients. MATERIAL AND METHOD: One thousand consecutive primary LTx patients were performed under tacrolimus between August 1989 and December 1992 were followed up until August 2004. Mean follow-up was 13.4 +/- 0.92 (range, 11.7-15) years. There were 600 males and 400 females with a mean age of 42.6 +/- 20.2 years. There were 166 children (age 18 years or younger) and 834 adults, of whom 204 were older than 60 years (seniors). RESULTS: Four hundred ninety-seven (49.7%) patients died in the follow-up period. The overall 15-year actuarial patient survival rate was 51.4%. The survival rate for children was significantly better (81.3%) compared with adults (47.5%) and seniors (36.4%) (P = .0001). One hundred fifty-one patients received a second LTx, 22 patients received a third LTx, and 4 patients received a fourth LTx. Over all 15 years the actuarial graft survival rate was 46.1%. At last follow-up, 69.1% of patients were off steroids. The majority of late deaths were due to age-related complications, recurrence of disease, and De novo cancers. CONCLUSION: The data on longitudinal follow-up have shown actuarial survival for children to be significantly better than in adults and seniors. Graft loss from immunological causes are rare even with long-term follow-up.

Adult↗
PubMed2004

Review article: current status of liver transplantation in HIV-infected patients.

The increases in survival of patients infected with human immunodeficiency virus is attributed to the introduction of combination human immunodeficiency virus antiviral therapy, better known as highly active anti-retroviral therapy. In fact, survival statistics have improved such that individuals often succumb to other disease entities, notably liver failure and not from acquired immunodeficiency syndrome complications. Liver transplantation has been introduction in this patient population in several centres around the world. This review will discuss the current clinical status of liver transplantation in individuals suffering from human immunodeficiency virus infection.

Antiretroviral Therapy, Highly Active↗
PubMed2004

Recurrent hepatitis C in liver allografts: prospective assessment of diagnostic accuracy, identification of pitfalls, and observations about pathogenesis.

RATIONALE AND DESIGN: The accuracy of a prospective histopathologic diagnosis of rejection and recurrent hepatitis C (HCV) was determined in 48 HCV RNA-positive liver allograft recipients enrolled in an "immunosuppression minimization protocol" between July 29, 2001 and January 24, 2003. Prospective entry of all pertinent treatment, laboratory, and histopathology results into an electronic database enabled a retrospective analysis of the accuracy of histopathologic diagnoses and the pathophysiologic relationship between recurrent HCV and rejection. RESULTS: Time to first onset of acute rejection (AR) (mean, 107 days; median, 83 days; range, 7-329 days) overlapped with the time to first onset of recurrent HCV (mean, 115 days; median, 123 days; range, 22-315 days), making distinction between the two difficult. AR and chronic rejection (CR) with and without co-existent HCV showed overlapping but significantly different liver injury test profiles. One major and two minor errors occurred (positive predictive values for AR = 91%; recurrent HCV = 100%); all involved an overdiagnosis of AR in the context of recurrent HCV. Retrospective analysis of the mistakes showed that major errors can be avoided altogether and the impact of unavoidable minor errors can be minimized by strict adherence to specific histopathologic criteria, close clinicopathologic correlation including examination of HCV RNA levels, and a conservative approach to the use of additional immunosuppression. In addition, histopathologic diagnoses of moderate and severe AR and CR were associated with relatively low HCV RNA levels, whereas relatively high HCV RNA levels were associated with a histopathologic diagnosis of hepatitis alone, particularly the cholestatic variant of HCV. CONCLUSIONS: Liver allograft biopsy interpretation can rapidly and accurately distinguish between recurrent HCV and AR/CR. In addition, the histopathologic observations suggest that the immune mechanism responsible for HCV clearance overlap with those leading to significant rejection.

Acute Disease↗
PubMed2002

Real-time monitoring of acute liver-allograft rejection using the Banff schema.

BACKGROUND: The Banff schema is the internationally accepted standard for grading acute liver-allograft rejection, but it has not been prospectively tested. METHODS: Complete Banff grading was prospectively applied to 2,038 liver-allograft biopsies from 901 adult tacrolimus-treated primary hepatic allograft recipients between August 1995 and September 2001. Histopathologic data was melded with demographic, clinical, and laboratory data into a database on an ongoing basis using locally developed software. RESULTS: Acute rejection developed in 575 of 901 (64%) patients and the worst grade was mild in 422 of 575 (73%). At least one episode of moderate or severe acute rejection developed in 153 of 901 (17%) patients and most episodes, irrespective of severity, occurred within the first year after transplantation. Patients with moderate or severe acute rejection showed higher alanine aminotransferase (P =0.007) and aspartate aminotransferase ( P=0.07) levels and were more likely to develop perivenular fibrosis on follow-up biopsies (P =0.001) and graft failure from acute or chronic rejection ( P=0.004) than those with mild rejection. Regardless of severity, 80% of patients with acute rejection did not develop significant fibrosis in follow-up biopsies, and graft failure from acute or chronic rejection occurred in only 11 of 901 (1%) allografts. CONCLUSIONS: Most acute-rejection episodes are mild and do not lead to clinically significant architectural sequelae. When tested prospectively under real-life and -time conditions, the Banff schema can be used to identify those few patients who are potentially at risk for more significant problems. Creation, capture, and integration of non-free text, or "digital," pathology data can be used to prospectively conduct outcomes-based research in transplantation.

Acute Disease↗
PubMed2001

De novo malignancies after liver transplantation: a major cause of late death.

1. Recurrent and de novo malignancies are the second leading causes of late death in liver transplant recipients, following age-related cardiovascular complications. 2. The increased incidence of de novo malignancies in liver transplant recipients compared with the general population reflects their demographic makeup, known preexistent risk factors for cancer, greater rate of chronic viral infection, and actions of exogenous immunosuppression. 3. The greatest incidence of de novo malignancies is seen in cancers associated with chronic viral infections, such as Epstein-Barr virus-associated posttransplant lymphoproliferative disease, and skin cancers, including squamous cell carcinoma and Kaposi's sarcoma. 4. Although a greater incidence of such malignancies as oropharyngeal malignancy and colorectal cancer was noted, there did not appear to be an increased risk for liver transplant recipients matched for age, sex, and length of follow-up using modified life-table technique and Surveillance Epidemiology End Result data with a similar at-risk group. However, they may present with more advanced stages of disease. 5. An increased incidence of de novo cancers in chronically immunocompromised liver transplant recipients demands careful long-term screening protocols to help facilitate diagnosis at an earlier stage of disease.

Humans↗
PubMed1999

Liver transplantation for Wilson's disease: a single-center experience.

Wilson's disease is a hereditary defect in copper excretion leading to the accumulation of copper in the tissues, with subsequent tissue damage. The most serious sequela is that of progressive central nervous system involvement. The use of orthotopic liver transplantation (OLT) has been controversial for those patients with neurological symptoms attributed to Wilson's disease. The aim of this study is to determine the effectiveness of OLT for patients with Wilson's disease, including those with neurological involvement attributed to copper accumulation in the central nervous system. OLT was performed in 45 patients (19 men [42.2%], 26 women [57.8%]) with Wilson's disease between 1971 and 1993 who were followed up for at least 4 years. The age at diagnosis of Wilson's disease ranged from 3 to 41 years (mean, 17.7 +/- 7.4 years). The age at OLT ranged from 8 to 52 years (mean, 22.3 +/- 9.4 years). Nineteen patients (42.2%) were aged younger than 18 years at OLT. The indications for OLT included chronic hepatic failure in 15 patients (33.3%) and fulminant (FHF) or subfulminant hepatic failure in 30 patients (66. 6%). All but 1 of the 19 pediatric patients (94.7%) were in the latter group. Twenty-five patients (55.5%) were receiving D-penicillamine, 9 patients for more than 1 year; none of the patients treated long term presented as FHF. Thirty-three patients (73.3%) survived more than 5 years after OLT. Fourteen patients (31%) died during the posttransplantation period; 7 of the 14 patients (50%) were aged younger than 18 years. Twelve patients died during the first 3 months after OLT of complications of disease and surgery, 10 of whom underwent transplantation for FHF. The other 2 patients died 6 and 9 years after transplantation of infectious problems. Eleven patients (24.4%) required retransplantation because of a primary nonfunctioning graft (n = 6), chronic rejection (n = 4), and hepatic artery thrombosis (n = 1). Seventeen patients (37.7%) presented with neurological abnormalities; 14 patients with Wilsonian neurological manifestations and 3 patients with components of increased intracranial pressure. Ten of the 13 surviving patients with hepatic insufficiency and neurological abnormalities at OLT showed significant neurological improvement. Our experience shows OLT is a life-saving procedure in patients with end-stage Wilson's disease and is associated with excellent long-term survival. The neurological manifestation of the disease can improve significantly after OLT. Earlier transplantation in patients with an unsatisfactory response to medical treatment may prevent irreversible neurological deterioration and less satisfactory improvement after OLT.

Adult↗
PubMed1999

Liver transplantation for metabolic liver diseases.

Liver transplantation has revolutionized the outcome of metabolic liver diseases that are caused by defects in hepatocytes (e.g., Wilson's disease) or by excessive deposition of substrates secondary to their increased absorption (e.g., hemochromatosis). Early diagnosis and referral are the keys to successful outcome. The timing of liver transplantation for patients on medical therapy depends on a lack of biochemical and clinical evidence of improvement. Overall outcome following liver transplantation depends on the severity of multisystem involvement and preoperative decompensation.

Hemochromatosis↗
PubMed1998

Expression of cytosolic beta-glucosidase in guinea pig liver cells.

The cytosolic beta-glucosidase of mammalian liver has been implicated in the metabolic transformation of plant glycosides, such as vicine and amygdalin, which are associated with the development of toxic syndromes. We investigated which cell types express cytosolic beta-glucosidase in guinea pig liver, and characterized the contribution of this enzyme to the hydrolysis of aromatic glucosides in cultured cells and in tissue slices. Cytosolic beta-glucosidase was expressed in hepatocytes and not in Kupffer or endothelial cells as determined by enzyme-specific activity and Western blots of liver cell extracts. Intracellular beta-glucosidase activity was visualized using the fluorescent beta-glucosidase substrate, resorufin beta-D-glucoside, and shown to be caused by the cytosolic beta-glucosidase using the inhibitors, conduritol beta-epoxide and dinitrophenol-2-deoxy-2-fluoro-beta-D-glucopyranoside (DNP2FGlc). Staining of fresh liver slices with resorufin beta-glucoside revealed that cytosolic beta-glucosidase is expressed in all hepatocytes, with no significant portal-central gradient. These data indicate that cytosolic beta-glucosidase is a hepatocyte-specific enzyme, and support the hypothesis that cytosolic beta-glucosidase in the liver functions to hydrolyze small glucosides absorbed by the intestine. Furthermore, toxic injury to cultured hepatocytes by CCl4 resulted in release of cytosolic beta-glucosidase in parallel with the hepatocyte marker enzymes alanine transaminase and lactate dehydrogenase. This suggests that acute increases in serum levels of cytosolic beta-glucosidase in animal models of liver injury may reflect direct injury of hepatocytes.

Animals↗
PubMed1998

Role of splenectomy in human liver transplantation under modern-day immunosuppression.

Between January 1987 and October 1991, 1466 patients underwent consecutive Orthotopic Liver Transplantation (OLTx) at the University of Pittsburgh. Forty of these patient's had concomitant splenectomy with OLTx. These patients were compared to 147 randomly selected OLTx patients without splenectomy within the same time period. One-year patient and graft survival (PS and GS) were lower in splenectomized (Splx) patients compared to nonsplenectomized (non-Splx) patients (59% vs 86% PS, 55% vs 80% GS, respectively). One-month and one-year patient mortality in the Splx group was higher than in the non-splx patients (20% vs 3.4%, P < 0.001 for one month; 40% vs 14.3%, P = 0.003 for one year, respectively). One-month and one-year sepsis-related mortality was also high in Splx patients (17.5% vs 2.7%, P = 0.0022, for one month, and 30% vs 11.5%, P = 0.0043, for one year, respectively). We conclude that concomitant splenectomy with OLTx has a significantly higher patient mortality mainly due to its septic complications and, at present, unless there is a specific indication for a splenectomy, the routine addition of this procedure to liver allograft surgery would not be recommended.

Adolescent↗
PubMed1997

Infectivity of hepatic allografts with antibodies to hepatitis B virus.

BACKGROUND: Since suitable recipients for hepatic allografts from donors with antibodies to hepatitis B virus (HBV) have not been determined, a review of our 7-year experience with donors positive for hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), or both was undertaken. METHODS: Recipients of hepatic allografts from donors with antibodies to HBV were identified by a retrospective review of procurement records and screened for HBV infection. RESULTS: From January 1, 1990, to January 1, 1997, 2578 liver transplants were performed and 140 (5.4%) recipients received an allograft from a donor with antibodies to HBV. Twenty-five of 48 recipients of a hepatic allograft from a donor positive only for anti-HBs were screened and none developed HBV infection. Twenty-five of 41 naive recipients of a hepatic allograft from an anti-HBc positive donor were screened and 18/25 (72%) developed HBV infection. Four of these 18 naive recipients with HBV infection received an allograft from a donor positive for both anti-HBc and anti-HBs. Seven of 13 anti-HBs-positive recipients of an allograft from an anti-HBc-positive donor were screened and none developed HBV infection. Fifteen of 16 recipients positive only for anti-HBc who received a hepatic allograft from an anti-HBc-positive donor were screened and 2/15 (13%) developed HBV infection. CONCLUSIONS: Hepatic allografts from donors positive only for anti-HBs do not transmit HBV infection. Hepatic allografts from anti-HBc-positive donors frequently transmit HBV infection to naive recipients regardless of the donor anti-HBs status, and antiviral prophylaxis may be indicated. Anti-HBs-positive recipients appear resistant to HBV infection after orthotopic liver transplantation with an allograft from an anti-HBc-positive donor. Recipients positive only for anti-HBc infrequently develop HBV infection when transplanted with an allograft from an anti-HBc-positive donor; however, HBV prophylaxis may be justified.

Hepatitis B↗
PubMed1995

Liver transplantation for HBV-related disease under immunosuppression with tacrolimus: an experience with 78 consecutive cases.

Hepatitis B viral liver disease (HBVLD) is a major worldwide health problem. It is estimated over 300 million people have had hepatitis B virus infection and that one-third of these have chronic HBVLD. Little effective therapy exists for HBVLD even though high dose interferon (IFN) has been advocated. For those who either are untreated or do not respond to IFN, HBVLD is steadily progressive and orthotopic liver transplantation (OLTx) is the only available therapy. Until quite recently, all OLTx recipients received cyclosporine (CyA) and prednisone. The consequence of OLTx for HBV disease in individuals immunosuppressed with tacrolimus has not previously been reported. A total of 78 consecutive patients with HBV-related liver diseases who were transplanted between January 1, 1990, and December 31, 1991, and treated with tacrolimus were studied. The clinical records of these patients were reviewed retrospectively. HBV disease recurrence was documented with serologic and histologic methods. As of April 1, 1993, 57 of 78 (73%) of the patients were still alive. Thirty-one of the alive patients have documented HBV recurrence. Eighteen of these 31 patients, however, have normal liver function. With a median follow-up of 24 months, 8 patients (10.9%) have died of recurrent HBVLD. Seven of 8 patients, who preoperatively were HBeAg+, developed recurrence and 4 of these patients have already died of recurrence. Patients who were HBsAg+ rarely recurred (1 of 16 patients). The use of HBIG did not prevent recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗